Atrial natriuretic peptide (ANP) is a protein secreted by heart muscle cells which regulates blood pressure and maintains plasma volume in healthy individuals by mediating natriuretic, diuretic and haemodynamic effects. Vessel dilator (VSDL) is a naturally occurring 37 amino acid cardiac peptide consisting of amino acids 31-67 of the 126 amino acid ANP. The main biological activity of VSDL is to regulate blood pressure and maintain plasma volume in healthy individuals by mediating natriuretic, diuretic and haemodynamic effects (Vesely, 2003).
Investigations into the use of VSDL for the treatment of cardiac diseases such as congestive heart failure (CHF) have been conducted via both preclinical and human clinical studies. It has been shown that VSDL can significantly improve haemodynamic and renal parameters, such as cardiac index/output, pulmonary capillary wedge pressure, systemic and pulmonary vascular resistance, natriuresis, diuresis, and creatinine clearance without any symptomatic side effects (Vesely, 1994 and 1998). VSDL is considered to be a safe and potential effective treatment by mediating beneficial haemodynamic effects including, but not limited to, beneficial natriuretic, diuretic and renal effects, through mechanisms of regulating plasma volume and blood pressure (BP) within clinically acceptable ranges and without seriously adverse side effects. Accordingly, VSDL can be administered to subjects with acute decompensated congestive heart failure (ADCHF). Moreover, VSDL has also been found to have anticancer effects (Skelton et al. 2011), and is a promising candidate in the treatment of acute renal failure (Vesely, 2003). Accordingly, it will be appreciated that VSDL is a useful candidate for the treatment of various diseases.
The present applicant has surprisingly found that when a human subject is dosed with VSDL a steady state blood plasma concentration (Css) of the active agent is not necessarily achieved in accordance with classical pharmacokinetic dosage calculations.